Current status of disease-modifying drugs in progressive rheumatoid arthritis.

Abstract

The goals of drug treatment in rheumatoid arthritis are twofold. Firstly, we attempt to suppress pain and inflammation with non-steroidal anti-inflammatory drugs (NSAIDs), at times augmented by low doses of corticosteroids. These agents are throught not to modify the course of rheumatoid arthritis (O'Brien, 1983; Pinals, 1983). Secondly, we attempt to induce remission if the disease progresses despite rest and NSAIDs to involve by pain and swelling mUltiple (typically more than 6) joints. Most rheumatologists begin treating progressive rheumatoid arthritis within a few months of onset and are unwilling to wait for the signal of radiological erosions. The repertoire of disease-modifying drugs is small, especially if we insist on compounds that have proven effectiveness in double-blind controlled studies. These agents are listed in table I along with their putative sites of action (Lipsky, 1983) and their documented effects on radiological erosions. Absent from this list are methotrexate and levamisole, because of inadequately controlled trials with the former and unacceptable toxicity in the latter. The 4 classes of compounds, although differing in chemical structure and pharmacology, have some features in common. The onset of clinical improvement with each takes months to begin, and relapse of disease may be expected within a few months of cessation. Historically, there is room for some optimism in the search for disease-modifying drugs. Gold compounds were probably first tried in rheumatoid arthritis in the mistaken belief that the disease was a manifestation of tuberculosis (Bunch and O'Duffy, 1980). The chloroquine derivatives were accidentally found to be beneficial (Page, 1951), and D-penicillamine was used because it could dissociate macroglobulins (Jaffe, 1962). The immunosuppressive agents azathioprine and cyclophosphamide were targeted at abnormal immunological events in rheumatoid arthritis, as evidenced by abnormal production of rheumatoid factors and the presence in synovial tissues of abnormal collections of lymphocytes. All these compounds have been proven clinically effective in rheumatoid arthritis in studies that rarely exceeded 1 year, and have been reviewed in detail elsewhere (Bunch and O'Duffy, 1980). In this article we examine the evidence for sustained benefits, i.e. beyond 1 year of use.